Resource utilization and treatment costs of patients with severe hemophilia A: Real-world data from the ATHNdataset.

Hemophilia A is characterized by unpredictable spontaneous bleeds and chronic comorbidities. However, limited data exists at the national level into detailed management patterns related to patient clinical characteristics, representative real-world dosing and treatment frequency, and costs. To assess and characterize the US severe hemophilia A (SHA) population, including subgroups of patients, in terms of clinical and demographic characteristics, healthcare resource utilization received at hemophilia treatment centers (HTCs), and projected annual costs of treatment utilizing data from the ATHNdataset of the American Thrombosis and Hemostasis Network (ATHN). Adult male people with SHA (PwSHA) (FVIII < 1%) were identified in the ATHNdataset between January 2013 and September 2019. This retrospective cohort study described patients' demographic and clinical characteristics, clinical history, as well as the HTC-related health resource utilization (HRU), treatment utilization, and projected annual treatment costs of US PwSHA received over the most recent year. Results are reported for the overall population and for three mutually exclusive subpopulations of patients: PwSHA with a history of and/or current inhibitors, PwSHA without a history of inhibitors but with (or a history of) one or more transfusion-transmitted infections (hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV]), and PwSHA without a history of inhibitors or of transfusion-transmitted infections (HBV, HCV, or HIV). Of the overall PwSHA cohort (N = 3677), there was a high prevalence of HCV (24.1%) and HIV (13.7%), while the prevalence of HBV (4.9%) was lower. Note that 20.5% of PwSHA overall currently or ever had FVIII inhibitors. On average, PwSHA had 2.8 total HTC visits per year, including 0.9 comprehensive care visits, 1.1 telephone contact visits, 0.5 office visits, and 0.1 surgeries or other procedures. However, 23.3% of PwSHA were not seen at an HTC, and 33.8% of PwSHA did not have a comprehensive care visit during their most recent year of data. HTC-related HRU was similar between the overall cohort and across the patient subpopulations, although PwSHA and inhibitors had more frequent HTC visits (a mean of 3.6 visits annually vs. 2.5-2.8 in the other groups). Using reported treatment frequency and dosing, estimated mean annual hemophilia treatment costs varied by treatment and across the three subpopulations: extended half-life factor product ($893,609-934,301 by subpopulation), standard half-life factor product ($798,700-930,812), plasma-derived factor product ($613,220-801,061), and non-factor product treatment ($765,289-833,240). This study summarized recent sociodemographic and clinical characteristics, HTC-related HRU, and HA treatments and projected costs among adult PwSHA, including among key subpopulations of PwSHA. PwSHA experience substantial clinical and resource burden on a chronic basis, despite the care coordination efforts of ATHN-affiliated HTCs. These findings motivate further exploration of the drivers of resource utilization, observed differences across subpopulations and other disparities, and ongoing monitoring of clinical and treatment burden in the face of an evolving care landscape.

Health care costs and resource utilization among commercially insured adult patients with hemophilia A managed with FVIII prophylaxis in the United States.

BACKGROUND: Standard of care for patients with severe hemophilia A (HA) is life-long prophylaxis with factor VIII (FVIII) concentrate or other hemostatic agents. Published literature highlights a wide range of treatment costs for patients with HA. OBJECTIVE: To estimate average annual health care costs and resource utilization for a cross-section of adult patients managed with FVIII concentrate prophylaxis using recent data from a large US commercial claims database. METHODS: Adult males with 1 or more claim with HA diagnosis, continuous commercial plan enrollment, and 4 or more FVIII prescription dispenses during 12 months were identified from IBM MarketScan Research Database from January 2013 to September 2019, excluding those with FVIII inhibitors, an HIV/AIDS diagnosis, or diagnosis and treatment for hepatitis B or C. Patients were classified as using FVIII prophylaxis if they met any of the following definitions: (1) 6 or more FVIII dispenses, (2) a gap of 60 days or less between dispenses, and (3) at least 273 days supply in the 12-month period. Additionally, subgroups of patients meeting each individual definition were examined, with some patients included in all 3 subgroups. RESULTS: The overall cohort included 411 patients who met 1 or more of the 3 definitions, with a mean age of 28.9 years. Subgroups of 401, 325, and 237 patients met the first, second, and third FVIII prophylaxis definitions, respectively. Per-patient mean (SD) annual all-cause health care costs were $654,571 ($380,762) in the overall cohort and ranged from $650,065 ($382,196) to $759,661 ($387,040) among subgroups. Cost of FVIII concentrate accounted for more than 96% of total costs in the overall cohort and in each subgroup. Cost of FVIII in the overall cohort varied according to type of concentrate, with the highest among patients who were treated with both standard and extended half-life (SHL and EHL) FVIII ($784,945), followed by EHL FVIII only ($708,928), SHL FVIII only ($647,800), and plasma-derived FVIII ($535,614). The most common treatment type was SHL FVIII only (45.7% of all patients). In the overall cohort, the majority had 1 or more outpatient visits (94.9%), while emergency department visits, hospital admissions, and home health visits occurred less frequently (27.0%, 7.1%, and 7.1%, respectively). CONCLUSIONS: Commercially insured patients with HA incur substantial all-cause annual health care costs, with FVIII concentrate accounting for a majority of costs. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc, which was involved in the protocol development, analysis plan development, data interpretation, manuscript preparation, and publication decisions. All authors contributed to protocol development, analysis plan development, data interpretation, and manuscript development and maintained control over the final content. Thornburg has received professional fees from BioMarin Pharmaceutical, CSL Behring, Genentech, Novo Nordisk, Sanofi Genzyme, HEMA Biologics, and Spark Therapeutics and institutional research funding from BioMarin Pharmaceutical, Novo Nordisk, and Sanofi Genzyme. Adamski, Cook, and Sendhil are employees of Analysis Group, a consulting company that was contracted by BioMarin Pharmaceutical to conduct this study and develop the manuscript. Vembusubramanian is a former employee of Analysis Group. Hinds, Chen, and Sammon are employees and shareholders of BioMarin Pharmaceutical. Solari is a former employee of BioMarin Pharmaceutical. Garrison has received consulting fees from BioMarin Pharmaceutical and Analysis Group. Croteau has received professional fees from BioMarin Pharmaceutical, Bayer, CSL Behring, HEMA Biologics, and Pfizer and institutional research funding from Novo Nordisk and Spark Therapeutics.

Health insurance coverage and switching among people with hemophilia A in the United States.

BACKGROUND: Hemophilia A (HA) is marked by substantial economic burden, including costs of ongoing treatment, increased monitoring, bleed events, and other health care utilization associated with managing the disease and comorbidities related to the disease. Gene therapies and other anticipated breakthrough treatments hold potential to substantially offset long-term traditional factor VIII (FVIII) prophylaxis in specific populations. Fragmentation of the US insurance system, however, may impact payers' approaches to coverage of new treatments, given concerns about patients "switching" insurance and the payer's ability to offset costs over time. OBJECTIVE: To assess insurance coverage and switching across payers among people with severe HA (SHA) using real-world data. METHODS: Adult men with SHA (FVIII measuring < 1%) in the American Thrombosis and Hemostasis Network dataset between January 2013 and September 2019 were identified. Patients' primary insurance category (ie, commercial, Medicaid, Medicare) and insurance switching over time were described. Outcomes included distribution of current primary insurance coverage by category and mean years of coverage per payer for commercially insured patients, including those with 2 or more commercial payers, and for those who switched insurance categories (eg, coverage by a commercial payer and government payer). RESULTS: Among the cohort of patients with SHA (N = 3,677), 51.9% had commercial primary insurance and 29.0% had coverage by Medicaid (including state-funded programs). The mean duration of follow-up in the database was 6.3 years for patients with at least 1 year of follow-up. Among patients who had ever been commercially insured, 74.9% had the same commercial payer for the entire follow-up period. The mean time covered by the same commercial insurance was 4.8 years. Only 7.5% of patients switched insurance categories (eg, from commercial to Medicaid). Among those who switched categories, patients averaged 3.9 years of commercial coverage, 4.0 years of Medicaid coverage, and 4.8 years of Medicare coverage during the follow-up period. CONCLUSIONS: Both commercially and government-insured patients with SHA typically maintain continuous coverage for extended periods, with limited switching between payers and insurance categories over time. These findings suggest that should breakthrough treatments be approved, payers would likely be able to realize substantial cost savings associated with avoiding long-term prophylactic therapies during the several years after treatment. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc. Hinds, Chen, and Sammon are employees of BioMarin Pharmaceutical Inc. and own stock/stock options. Solari was an employee of BioMarin Pharmaceutical Inc. at the time of the study. Pezalla is CEO of Enlightenment Bioconsult, LLC. He, Cheng, and Recht are, or were at the time of this study, employees of American Thrombosis and Hemostasis Network (ATHN), which has received ATHNdataset licensing and other fees from BioMarin Pharmaceutical Inc. Research funding to Recht's employers has come from Bayer, BioMarin Pharmaceutical Inc., CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda, and uniQure. Recht has also worked as a consultant for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure; sits on the board of directors of the Foundation for Women and Girls with Blood Disorders and of Partners in Bleeding Disorders; and is an employee of the Oregon Health & Science University. Data from this study were presented as a poster at AMCP Nexus 2021; October 18-21, 2021; Denver, CO.

Ex vivo MRI facilitates localization of cerebral microbleeds of different ages during neuropathology assessment.

Cerebral microbleeds (CMBs) identified by in vivo magnetic resonance imaging (MRI) of brains of older persons may have clinical relevance due to their association with cognitive impairment and other adverse neurologic outcomes, but are often not detected in routine neuropathology evaluations. In this study, the utility of ex vivo MRI in the neuropathological identification, localization, and frequency of CMBs was investigated. The study included 3 community dwelling elders with Alzheimer's dementia, and mild to severe small vessel disease (SVD). Ex vivo MRI was performed on the fixed hemisphere to identify CMBs, blinded to the neuropathology diagnoses. The hemibrains were then sliced at 1 cm intervals and 2, 1 or 0 microhemorrhages (MH) were detected on the cut surfaces of brain slabs using the routine neuropathology protocol. Ex vivo imaging detected 15, 14 and 9 possible CMBs in cases 1, 2 and 3, respectively. To obtain histological confirmation of the CMBs detected by ex vivo MRI, the 1 cm brain slabs were dissected further and MHs or areas corresponding to the CMBs detected by ex vivo MRI were blocked and serially sectioned at 6 µm intervals. Macroscopic examination followed by microscopy post ex vivo MRI resulted in detection of 35 MHs and therefore, about 12 times as many MHs were detected compared to routine neuropathology assessment without ex vivo MRI. While microscopy identified previously unrecognized chronic MHs, it also showed that MHs were acute or subacute and therefore may represent perimortem events. Ex vivo MRI detected CMBs not otherwise identified on routine neuropathological examination of brains of older persons and histologic evaluation of the CMBs is necessary to determine the age and clinical relevance of each hemorrhage.

Early experiences of nusinersen for the treatment of spinal muscular atrophy: Results from a large survey of patients and caregivers.

BACKGROUND: This study aimed to examine the early experience of nusinersen for spinal muscular atrophy (SMA) from the patient and caregiver perspective. METHODS: A 54-item online survey was administered to adult patients and caregivers of pediatric patients diagnosed with SMA. RESULTS: Overall, respondents (56 patients and 45 caregivers) were satisfied with nusinersen. Satisfaction was highest on changes in energy, stamina, and motor function and lowest on treatment administration and overall time commitment. Differences were noted for treatment effect sustained over time as reported by adult patients vs caregivers reporting on behalf of pediatric patients. Respondents reported insurance approval as a key barrier to access, particularly among adult patients. CONCLUSIONS: Despite therapeutic advances, there remain significant unmet needs for SMA. Challenges with administration and barriers to access potentially limit the number of patients treated or delay treatment. Continued efforts are needed to develop more treatment options and to improve access to treatments.

Assessment of Bactrocera dorsalis (Diptera: Tephritidae) Diets on Adult Fecundity and Larval Development: Insights Into Employing the Sterile Insect Technique.

Bactrocera dorsalis (Hendel) is a notorious insect pest that attacks diverse vegetables and fruits worldwide. The sterile insect technique has been developed as an environmentally friendly and effective control method that depends on the mass production of target flies. Because dietary yeast (protein) and sucrose (carbohydrate) are important in adult diets, yeast:sucrose (Y:S) mixtures are crucial for the mass-rearing of B. dorsalis. In this study, we found adult diets with different ratios of yeast to sucrose-influenced fecundity, and an extremely high or low Y:S ratios significantly decreased egg production of B. dorsalis. Additionally, the maximum oviposition efficiency was realized at dietary yeast to sucrose ratios of 1:1 and 1:3, suggesting their potential use to produce more eggs for the mass production of B. dorsalis. Here, new gel diets having different yeast concentrations (g/L water) were also assessed for rearing B. dorsalis larvae. Gel diets containing 20 g/L yeast led to a higher pupation, pupal weight and adult eclosion rate, and a shorter developmental time than other yeast concentrations. Moreover, the present gel diet also resulted in greater pupal production and adult emergence rates than previously used liquid and solid artificial diets, revealing that it is suitable for rearing B. dorsalis larvae. This research provides a useful reference on artificial diets mixtures for mass rearing B. dorsalis, which is critical for employing the sterile insect technique.

Healthcare Utilization, Costs of Care, and Mortality Among Patients With Spinal Muscular Atrophy.

Objectives: To understand treatment patterns, healthcare resource utilization, and costs of care among patients with spinal muscular atrophy (SMA). Methods: SMA patients were identified from a large managed care population using administrative claims data from January 2006 to March 2016. Patients were classified into infantile, childhood-onset, and late-onset groups based on age of first SMA diagnosis. They were matched 1:1 to non-SMA patients based on age, gender, geography, and health plan type. Results: In the infantile group, 17.4% and 26.1% were treated with invasive and non-invasive ventilation, respectively. Uses of orthotics/orthoses and orthopedic surgery were frequent: 54.5% and 22.7% childhood group; 27.0% and 38.5% late-onset group. Mean per member per month costs in SMA vs. matched non-SMA patients was $25,517 vs. $406 (infantile); $6,357 vs. $188 (childhood-onset); $2,499 vs. $742 (late-onset). Conclusions: SMA patients, particularly with infantile onset, incurred significantly higher healthcare utilization and costs than the general population.

Healthcare Utilization, Costs of Care, and Mortality Among Psatients With Spinal Muscular Atrophy.

OBJECTIVES: To understand treatment patterns, healthcare resource utilization, and costs of care among patients with spinal muscular atrophy (SMA). Methods: SMA patients were identified from a large managed care population using administrative claims data from January 2006 to March 2016. Patients were classified into infantile, childhood-onset, and late-onset groups based on age of first SMA diagnosis. They were matched 1:1 to non-SMA patients based on age, gender, geography, and health plan type. RESULTS: In the infantile group, 17.4% and 26.1% were treated with invasive and non-invasive ventilation, respectively. Uses of orthotics/orthoses and orthopedic surgery were frequent: 54.5% and 22.7% childhood group; 27.0% and 38.5% late-onset group. Mean per member per month costs in SMA vs. matched non-SMA patients was $25,517 vs. $406 (infantile); $6,357 vs. $188 (childhood-onset); $2,499 vs. $742 (late-onset). CONCLUSIONS: SMA patients, particularly with infantile onset, incurred significantly higher healthcare utilization and costs than the general population.

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.

The financial burden and health care utilization patterns associated with amnestic mild cognitive impairment.

INTRODUCTION: Individuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia. METHODS: With data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross-sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns. RESULTS: Patients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < .001) and were also significantly less likely to have been hospitalized (P = .04) and admitted to nursing home (P < .001). Compared to individuals with normal cognition, patients with aMCI had significantly less household income (P = .018). DISCUSSION: Patients with aMCI had lower medical expenditures than patients with AD dementia. Poor cognitive status was linearly associated with lower household income, higher medical expenditures, higher likelihood of nursing and home care services, and lower likelihood of outpatient visits.

A Cost-Effectiveness Analysis of Clopidogrel for Patients with Non-ST-Segment Elevation Acute Coronary Syndrome in China.

INTRODUCTION: There are a number of economic evaluation studies of clopidogrel for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) published from the perspective of multiple countries in recent years. However, relevant research is quite limited in China. We aimed to estimate the long-term cost effectiveness for up to 1-year treatment with clopidogrel plus acetylsalicylic acid (ASA) versus ASA alone for NSTEACS from the public payer perspective in China. METHODS: This analysis used a Markov model to simulate a cohort of patients for quality-adjusted life years (QALYs) gained and incremental cost for lifetime horizon. Based on the primary event rates, adherence rate, and mortality derived from the CURE trial, hazard functions obtained from published literature were used to extrapolate the overall survival to lifetime horizon. Resource utilization, hospitalization, medication costs, and utility values were estimated from official reports, published literature, and analysis of the patient-level insurance data in China. To assess the impact of parameters' uncertainty on cost-effectiveness results, one-way sensitivity analyses were undertaken for key parameters, and probabilistic sensitivity analysis (PSA) was conducted using the Monte Carlo simulation. RESULTS: The therapy of clopidogrel plus ASA is a cost-effective option in comparison with ASA alone for the treatment of NSTEACS in China, leading to 0.0548 life years (LYs) and 0.0518 QALYs gained per patient. From the public payer perspective in China, clopidogrel plus ASA is associated with an incremental cost of 43,340 China Yuan (CNY) per QALY gained and 41,030 CNY per LY gained (discounting at 3.5% per year). PSA results demonstrated that 88% of simulations were lower than the cost-effectiveness threshold of 150,721 CYN per QALY gained. Based on the one-way sensitivity analysis, results are most sensitive to price of clopidogrel, but remain well below this threshold. CONCLUSION: This analysis suggests that treatment with clopidogrel plus ASA for up to 1 year for patients with NSTEACS is cost effective in the local context of China from a public payers' perspective. FUNDING: Sanofi China.

The revised Atlanta criteria 2012 altered the classification, severity assessment and management of acute pancreatitis.

BACKGROUND: The Atlanta criteria for acute pancreatitis (AP) has been revised recently. This study was to evaluate its practical value in classification of AP, the severity assessment and management. METHODS: The clinical features, severity classification, outcome and risk factors for mortality of 3212 AP patients who had been admitted in Ruijin Hospital from 2004 to 2011 were analyzed based on the revised Atlanta criteria (RAC) and the original Atlanta criteria (OAC). RESULTS: Compared to the OAC group, the incidence of severe acute pancreatitis (SAP) was decreased by approximately one half (13.9% vs 28.2%) in the RAC group. The RAC presented a lower sensitivity but higher specificity, and its predictive value for severity and poor outcome was higher than those of the OAC. The proportion of SAP diagnosis and ICU admission in the early phase in the RAC group was significantly lower than that in the OAC group (P<0.05). Based on the RAC, the risk factors for death among SAP patients were older age, high CT severity index (CTSI), renal failure, cardiovascular failure, acute necrotic collection and walled-off necrosis. Compared to the OAC, the acute physiology and chronic health evaluation II (APACHE II) score, Ranson score, idiopathic etiology, respiratory failure and laparotomy debridement were not risk factors of death in contrast to walled-off necrosis. Interestingly, hypertriglyceridemia-related SAP had good outcomes in both groups. CONCLUSIONS: The RAC showed a higher predictive value for severity and poorer outcome than the OAC. However, the RAC resulted in fewer ICU admissions in the early phase due to its lower sensitivity for diagnosis of SAP. Among SAP cases, older age, high CTSI, renal and cardiovascular failure, complications of acute necrotic collection and walled-off necrosis were independent risk factors for mortality.

Medicare Expenditures of Individuals with Alzheimer's Disease and Related Dementias or Mild Cognitive Impairment Before and After Diagnosis.

OBJECTIVES: To characterize Medicare expenditure and usage trends in individuals with a coded diagnosis of Alzheimer's disease and related dementia (ADRD) or mild cognitive impairment (MCI) during the periods leading up to and after diagnosis. DESIGN: Retrospective observational cohort study. SETTING: Five percent sample of the 2009 to 2013 Medicare claims files. PARTICIPANTS: Individuals newly diagnosed with ADRD (n = 25,916) or MCI (n = 2,784), each with a propensity-score matched control subject. MEASUREMENTS: Medicare expenditures and usage during the 24 months before and after a new diagnosis of ADRD or MCI. RESULTS: Medicare expenditures were 42% higher in participants with ADRD ($10,622 vs $15,091, P < .001) and 41% higher in those with MCI ($9,728 vs $13,691, P < .001) during the year before diagnosis than in matched controls. Medicare expenditures of participants with ADRD increased to $27,126 for the first 12 months immediately after diagnosis and decreased to $17,257 during the 12 months after that. For participants with MCI, average Medicare expenditures were $20,386 for the 12 months after diagnosis and $14,286 for the 12 months after that. Use of inpatient care, postacute skilled nursing facility care, and home health care increased substantially after diagnosis of ADRD or MCI. CONCLUSION: Participants with ADRD and MCI incurred significantly higher Medicare expenditures than matched controls, even before they received a formal diagnosis. Medicare expenditures of individuals with ADRD and MCI may start to increase at least 12 months before their diagnosis, peak during the first few months immediately after diagnosis, and decrease afterward but remain at a higher level than before diagnosis. These findings highlight the importance of early diagnosis and indicate the need for complex case management to coordinate care transitions for individuals with ADRD and MCI.

Cost-effectiveness of recombinant tissue-type plasminogen activator within 3 hours of acute ischemic stroke: current evidence.

BACKGROUND AND PURPOSE: Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA. METHODS: A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies. Cost data, inflated to 2013 dollars, were based on drug wholesale acquisition cost and the literature. To compare r-tPA to no r-tPA, we calculated incremental total direct costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratios. We performed 1-way and probabilistic sensitivity analyses to evaluate uncertainty in the results. RESULTS: r-tPA resulted in a gain of 0.39 quality-adjusted life years (95% confidence range, 0.16-0.66) on average per patient and a lifetime cost-saving of $25,000 (95% confidence range, -$42,500 to -$11,000) compared with no r-tPA. In probabilistic sensitivity analyses, r-tPA was dominant compared with no r-tPA in ≈100% of simulations. The model was sensitive to inputs for r-tPA efficacy, healthcare costs for disabled patients, mortality rates for disabled and nondisabled patients, and quality of life estimates. CONCLUSIONS: Our analysis supports earlier economic evaluations that r-tPA is a cost-effective method to treat stroke. Appropriate use of r-tPA should be prioritized nationally.

Comparison of hospital length of stay, costs, and readmissions of alteplase versus catheter replacement among patients with occluded central venous catheters.

BACKGROUND: Central venous catheter (CVC) occlusion is common, affecting 30% of all CVCs. OBJECTIVE: To compare length of stay (LOS), costs, and readmissions associated with the use of alteplase to clear catheter blockage to outcomes associated with catheter replacement. DESIGN: Retrospective observational study utilizing a large hospital database. PARTICIPANTS: Hospitalized patients treated for catheter occlusion from January 2006 to December 2011. MAIN MEASURES: Univariate analyses of patient characteristics and treatment patterns and multivariable regression analyses of postocclusion hospital costs, LOS, and 30- and 90-day readmissions were conducted. KEY RESULTS: We included 34,579 patients treated for a CVC occlusion by replacement (N=1028) or by alteplase (2 mg) administration (N=33,551). Patients receiving alteplase were somewhat younger than those having catheter replacement (60 ± 19 vs 62 ± 20 years old, P=0.0002). After adjusting for patient and hospital factors via regression modeling, average daily postocclusion costs were $317 lower for alteplase recipients than for catheter replacement patients (95% confidence interval [CI]: 238.22-392.24; P<0.0001). Adjusted total postocclusion costs were $1419 lower for alteplase recipients versus patients receiving catheter replacement (95% CI: 307.27-2458.12; P=0.0121). Postocclusion operating room/surgery, radiology, and supply costs were significantly lower for alteplase recipients (P<0.001). Average adjusted postocclusion LOS was similar for both groups (P>0.05). Odds of readmission were not significantly different at 30 or 90 days. CONCLUSIONS: Among patients treated for an occluded CVC, alteplase-treated patients had lower daily and total postocclusion costs than patients receiving catheter replacement. Cost differences were mainly driven by lower operating room/surgery, radiology, and supplier costs.

Economic impact on US Medicare of a new diagnosis of myelodysplastic syndromes and the incremental costs associated with blood transfusion need.

BACKGROUND: Recent retrospective studies suggest myelodysplastic syndromes (MDSs) are more common than previously recognized and patients who develop transfusional dependence may be at risk for increased comorbid complications. STUDY DESIGN AND METHODS: A retrospective review was undertaken of Medicare claims focusing on costs associated with patients with a new claim listing ICD-9-CM Diagnosis Code 238.7 in first quarter of 2003. Patients were followed until 2005 to assess resource use and costs. RESULTS: A total of 512 patients aged 65 years or more with newly diagnosed MDS were identified. Forty percent had received red blood cell transfusions between 2003 and 2005. During the 3-year follow-up, transfused patients experienced increased prevalence of cardiac diseases, dyspnea, and infections. Cumulative 3-year mean Medicare costs for MDS patients were $49,156. Transfused patients had greater use of hospital inpatient and outpatient services and incurred significantly higher mean costs than nontransfused patients ($88,824 vs. $29,519, p < 0.001). After adjustment for baseline characteristics and clinical complications, transfusion was independently associated with a 48% increase in monthly costs in addition to the cost of transfusion administration. CONCLUSION: MDS places a significant economic burden on the US Medicare system. MDS patients requiring transfusions experience higher prevalence of new comorbid conditions and incur significantly higher Medicare costs than nontransfused patients during the initial 3 years after diagnosis.

Sleep apnea testing and outcomes in a large cohort of Medicare beneficiaries with newly diagnosed heart failure.

RATIONALE: Previous studies have demonstrated a high prevalence of sleep apnea (SA) in patients with chronic heart failure (HF), which is associated with higher rates of morbidity, mortality, and health care use. OBJECTIVES: To investigate the reported incidence, treatment, outcomes, and economic cost of SA in new-onset HF in a large U.S. database. METHODS: This retrospective cohort study used the 2003 to 2005 Medicare Standard Analytical Files and included subjects with newly diagnosed HF from the first quarter of 2004, without prior diagnosis of SA, stratified by testing, diagnosis, and treatment status. MEASUREMENTS AND MAIN RESULTS: Among a study population of 30,719 incident subjects with HF, only 1,263 (4%) were clinically suspected to have SA. Of these, 553 (2% of the total cohort) received SA testing, and 545 received treatment. After adjustment for age, sex, and comorbidities, subjects with HF who were tested, diagnosed, and treated for SA had a better 2-year survival rate compared with subjects with HF who were not tested (hazard ratio, 0.33 [95% confidence interval, 0.21-0.51], P < 0.0001). Similarly, among subjects who were tested and diagnosed, those who were treated had a better 2-year survival rate than those who were not treated (hazard ratio, 0.49 [95% confidence interval, 0.29-0.84], P = 0.009). CONCLUSIONS: In Medicare beneficiaries with HF, comorbid SA is most often not tested and consequently subjects are underdiagnosed and not treated. Meanwhile, in the few subjects in whom a diagnosis of SA is established and treatment is executed, survival improves significantly. These results support the importance of SA testing and treatment for patients newly diagnosed with HF.

Burden of illness of diabetic macular edema: literature review.

OBJECTIVE: To provide an overview of the literature on the burden of diabetic macular edema (DME) in the United States and selected European countries. RESEARCH DESIGN AND METHODS: Computerized searches of English-language literature were conducted in PubMed/MEDLINE (1980-2009). The searches were supplemented with electronic and manual searches of relevant society/association proceedings and bibliographies of electronically identified sources. Abstracts were reviewed for relevance to any of the following topics: epidemiology, including prevalence and incidence; health outcomes; resource use and treatment patterns; and economic and humanistic burden associated with DME. Relevant full text articles were retrieved and major findings were synthesized and compared within and across countries. RESULTS: A total of 400 citations were included in the initial review. After abstract screening, 47 articles were deemed pertinent and summarized in this review. The prevalence of DME among diabetic patients ranged from 0.85% to 12.3% across the countries studied. The prevalence and incidence of DME vary depending on type of diabetes (1 vs. 2), insulin- vs. non-insulin-dependence, and duration of disease (years since diagnosis). Although literature findings are limited and indicate a need for further investigation, a synthesis of the available results indicates that DME has a negative impact on patients' health-related quality of life. In addition, patients with DME consume significantly more healthcare resources and incur higher costs compared to diabetic patients without retinal complications. CONCLUSIONS: There remains a need for consistent data capture and assessment within and between countries included in this analysis. Despite the limited evidence, DME appears to be a costly disease that has a negative impact on patients' quality of life.

Surgical treatment patterns among Medicare beneficiaries newly diagnosed with lumbar spinal stenosis.

BACKGROUND CONTEXT: Lumbar spinal stenosis (LSS) is a prevalent degenerative condition in the elderly that can be managed medically or with surgical treatments. Recent studies have shown an increase in the utilization of surgery in the United States and great regional variations. An understanding of treatment patterns and costs in a population-based setting will help identify subgroup differences to help inform strategies for optimal care in patients with LSS. PURPOSE: This study sought to examine surgical treatment rate and types, time to treatment, and patient characteristics that affect treatment patterns for newly diagnosed LSS in the US Medicare population. STUDY DESIGN: A retrospective longitudinal study of administrative claims was performed on a 5% randomly selected sample of Medicare beneficiaries. PATIENT SAMPLE: Six thousand two hundred sixty-five Medicare beneficiaries newly diagnosed with LSS in the first quarter of 2003 were identified and followed until the end of 2005. OUTCOME MEASURES: Rate of LSS surgery, type and timing of LSS surgery, and Medicare costs. METHODS: A "de novo" LSS patient cohort was defined as those with claims with a primary diagnosis of LSS during the period of January to March 2003, excluding those with a LSS diagnosis in 2002. These patients were stratified into surgery and nonsurgery cohorts based on the presence of procedure codes for LSS surgery. The surgery cohort was further divided into three subgroups: laminectomy or laminotomy only; fusion only; and fusion with laminectomy or laminotomy. All Medicare claims for these patients were extracted and reviewed through December 2005. Descriptive statistics were carried out for demographic characteristics, comorbidities, treatment rates, and Medicare costs. RESULTS: This study indicated that 21% of LSS patients underwent surgery within 3 years of initial diagnosis. Surgery skews toward the healthier and younger patients. Overall, 78% of LSS surgeries were performed in the year of diagnosis, 13% in the second, and 9% in the third. Although laminectomies and laminotomies were the most frequently performed procedures across all years, a higher percentage of fusions were performed in addition to laminectomy or laminotomy in the second or third years after diagnosis than in the first year. The 3-year Medicare payments were $49,624 in the surgery cohort in comparison with $36,691 in the nonsurgery cohort. Patients who underwent a laminectomy/laminotomy alone incurred significantly lower Medicare payments ($42,293) than those who had fusion alone ($57,171) or laminectomy/laminotomy plus fusion ($63,555). CONCLUSIONS: The surgical management of LSS varies with respect to timing and type of surgery provided. Such variation needs to be explained beyond demographic and comorbid factors.